The dbl oncogene product contains a 238 amino acids domain, DH, which is shared by an expanding family of growth regulatory proteins. The DH, itself, as well as the whole dbl product when expressed and purified as a recombinant protein, stimulate GDP dissociation from purified, recombinant CDC42Hs and rhoA. These findings demonstrate that dbl can act as a GEF for more than one rho-like protein and establish that the minimal unit on dbl that is critical to its transforming function also directly regulates its GDP-GTP exchange activity. More recently, in vitro and in vivo studies establish that the DH is not sufficient by itself when expressed in NIH/3T3 cells to induce transformation. Sequences downstream of the DH comprising the PH domain are necessary for such activity. Studies are being carried out in order to establish the role of the PH domain in dbl-induced transforming activity. Comparison was made between the transforming activities of vav, an oncogene whose protein shares significant sequence similarity with the catalytic domain of the dbl product, and dbl with those of oncogenic ras and ras signal transduction pathways. GRF, but not vav or dbl, transformation is indistinguishable from oncogenic ras transformation. Instead, the strong similarities between rhoA transformation and vav and dbl transformation are more consistent with the possibility that the dbl family of oncogenes cause transformation via deregulated rho protein function.